Transcriptional response of mice infected with H9N2 or H7N9

Type I interferon (IFN) is the first line of defense against virus infection. By using both in vivo and in vitro influenza infection models, we found that type I IFN-κ, limited the replication of influenza viruses by stimulating a IFNAR-MAPK-cFos-CHD6 axis. Similarly, Zika virus (ZIKV) was also highly sensitive to IFN-κ-mediated suppression. With an IAV infected mouse model, we found that IFN-κ was the earliest responding type I interferon among all known members in mice after H9N2 infection, a low-pathogenic Avian Influenza, whereas this early induction did not occur upon highly pathogenic H7N9 infection. IFN-κ can efficiently contain both low- and high-pathogenic influenza replication in cultured human lung cells, and CHD6 was the major effector responsive molecule for IFN-κ, but not for IFN-α/β. Furthermore, we discovered that both IFNAR1 and IFNAR2 subunits of type I interferon receptor and their downstream axis of p38-cFos are engaged in IFN-κ signaling cascade to acti vate CHD6, which didn`t require STAT1 activity. In addition, we showed that the pre-treatment with IFN-κ before IAV challenge protected mice from high mortality. Altogether, our study identified an IFN-κ-specific pathway that suppressed influenza A virus in vitro and in vivo. Thus, IFN-κ may have potential as a new prevention and treatment agents against emerging viruses Mice were intranasally (i.n) inoculated with either 3.5x10e5 TCID50 of H7N9 virus, or 1.7x10e7 EID50 of H9N2 virus, or PBS (control group) in a volume of 50 microliters Infected mice were sacrificed at various time points ranging from 6hrs to day 14 post virus challenge for collection of lung tissues from which RNA were extracted and analyzed. Mice challenged with H7N9 IAV, H9N2 IAV, or PBS. 3 mice were pooled at indicated time for immune response analysis